1. Field of the Invention
The present invention relates to synthetic biological membranes with self organizing characteristics, and more particularly, the invention relates to membrane-mimetic liquid crystalline gels which change shape and function as a response to environmental changes.
2. Background of the Invention
In recent years, there has been increasing interest in the development of so-called xe2x80x9cintelligentxe2x80x9d or xe2x80x9csmartxe2x80x9d materials whose properties change in response to such environmental conditions as ionic strength, temperature, and magnetic- or electric-fields. The ability to control the structure and therefore the function of materials by application of external stimuli forms the basis of molecular machines, chemical valves and switches, sensors, and a wide range of optoelectronic materials.
Considerable effort is being expended to develop smart materials which can serve as vehicles to transport biological and non-biological materials. One such material is composed of a mixture of lipids, a low molecular weight polyethylene glycol-derived polymer lipid, and a pentanol surfactant. Warrnier, H. E. et al Science, (1996), 271, pp969-973. These gels change to a liquid by heating to a higher temperature. However, both the pentanol surfactant and elevated temperatures cause rapid degeneration of incorporated proteins and other biomolecules in the materials. Also, the material appears to undergo phase separation at reduced temperature. Lastly, the material does not seem to react to external stimuli other than temperature variations.
A need exists in the art for a material that is responsive to a variety of environmental stimuli. The material should be capable of transporting and/or spatially organizing biological components. The material should be comprised of matter, and exhibit physicochemical properties (e.g. phase changes) that are compatible to the biological material or to the target for the biological material. And the material should exhibit phase changes which are reversible.
It is the object of the present invention to provide a smart gel which over comes many of the disadvantages of the prior art.
Another object of the present invention is to provide a fluid which undergoes macroscopically observable structural and functional changes in response to an environmental stimulus, or to a myriad of environmental stimuli. A feature of the invention is its existence as a gel at relatively high temperatures, and its existence as a liquid at low temperatures. An advantage of the invention is its use as a drug delivery system wherein the high temperature point of the system is the body temperature of a target organism or target structure.
Another object of the present invention is to provide a biocompatible, membrane-mimetic liquid-crystalline material. A feature of this invention is the ability to package or encapsulate biologically active membrane proteins, membrane-associated biomolecules within an organized lipid matrix. An advantage of the invention is its use to encapsulate and spatially organize proteins, biomolecules, organics, and inorganic material while simultaneously protecting these encapsulated entities from degradation. This capability allows the invented mixture to produce and/or deliver membrane bound molecules or associated molecules, protected in the matrix, in their biologically or functionally active states in drug delivery applications, and in organized lipid-based arrays for device and assay applications.
Still another object of the present invention is to provide a mixture which provides functional characteristics in response to certain environmental stimuli, when certain structural characteristics are induced by other environmental stimuli. A feature of the invention is that macroscopic ordering of molecules occurs when a magnetic field, an electric field, or shear is applied to the mixture, but only when the mixture is at a certain temperature. An advantage of the invention is that such synergy between stimuli renders the mixture as a multi-positional or multi-variable switch.
Yet another object of the present invention is to provide a mixture which reacts to external stimuli to provide both structural and functional characteristics. A feature of the invention is that it manifests a birefringent phase when subjected to a certain environment, an optically isotropic (nonbirefringent) or transparent phase when subjected to another environment, and the ability to display visual confirmation of intact membrane structure associated with the birefringent phase. An advantage of the invention is an optical cue that an intact membrane has formed in response to application of certain stimuli.
Briefly, the invention provides for a material which undergoes a thermoreversible phase change, the material comprising a mixture of a lipid, a polymer amphiphile (such as a polymer-grafted phospholipid), a co-surfactant, and water.
Also provided is a method for delivering, encapsulating and/or transporting medicaments to a patient, the method comprising combining the medicaments with a liquid phase solution at a predetermined temperature to create a liquid mixture; increasing the temperature of the mixture to a second predetermined temperature so as to cause the mixture to solidify; and administering the solidified mixture to the patient.
The invention also provides a material which undergoes a thermoreversible phase change, the material comprising 65 to 90 percent by weight of water, 3 to 5 weight percent of surfactant, 7 to 27 weight percent lipid plus amphiphilic polymer, wherein the amount of polymer to lipid is approximately 4 to 10 mole percent.